There are a wide range of neurological and psychological disorders for which treatment may be provided by various means. For many disorders, administration of pharmaceutical agents is the most common treatment modality. In cases in which the symptoms of the disorder are resistant to pharmacological treatment or for which no pharmacological treatment exists, other modalities may be used, including neurostimulation.
Neurostimulation is a method of disease treatment which uses an electrical stimulator to provide a current signal which is used to stimulate the central nervous system (CNS), generally either directly or by means of a nerve of the peripheral nervous system. Such neurostimulators and their corresponding electrodes are generally implanted in a patient's body. There are currently two primary methods of neurostimulation for central nervous system disorders; deep brain stimulation (DBS) and vagus nerve stimulation (VNS). DBS uses an electrode implanted directly in a patient's brain, while VNS stimulates a patient's vagus nerve peripherally.
A commercially available DBS neurostimulator is manufactured and sold by Medtronic Inc. of Minneapolis, Minn., USA, model 3386, having a stimulating lead with four cylindrical stimulating electrodes. The deep brain stimulator is a surgically implanted medical device, similar to a cardiac pacemaker, which delivers high-frequency, pulsatile electrical stimulation to precisely targeted areas within the brain. The device consists of a very small electrode array (electrodes 1.5 mm in length with 3 mm center to center separation) placed in a deep brain structure and connected through an extension wire to an electrical pulse generator surgically implanted under the skin near the collarbone. The Medtronic DBS has received marketing clearance from the US Food and Drug Administration (FDA) with an indication for treatment of Parkinson's Disease, Essential Tremor, and Dystonia. Current research is evaluating DBS as a treatment for epilepsy, psychiatric disorders, and chronic pain.
The DBS stimulator is surgically placed under the skin of the chest of the patient. The stimulating DBS electrode lead is connected to the DBS stimulator wires and is placed in a specific inter-cranial location which may vary depending on the region of the brain being treated. The DBS system is adjusted by several parameters: 1. location of the 4 electrode lead, 2. selection of the stimulating electrodes, 3. amplitude of the stimulator signal, 4. frequency (repetition rate) of the stimulator signal, 5. polarity of the stimulating signal, and 6. pulse width of the stimulating signal. Post-implantation, all of these parameters except electrode location can be non-invasively varied by a clinician to enhance therapeutic effectiveness and minimize side effects. Amplitude, measured in volts, is the intensity or strength of the stimulation. The typical range is 1.5 to 9 volts. Frequency is the repetition rate at which the stimulation pulse is delivered and is measured in pulses per second (Hz); it typically ranges from 100-185 Hz. The pulse width is the duration of the stimulation pulse, measured in microseconds. The typical pulse width ranges from 60-120 microseconds.
Another commercially available neurostimulator is designed for use on the peripheral nervous system, specifically the vagus nerve. An example of this type of system is designed and sold by Cyberonics Corporation of Houston, Tex., USA. The Vagus Nerve Stimulator (VNS) Therapy device is implanted in a patient's chest under the skin immediately below the collarbone or close to the armpit. Two tiny wires from the device wrap around the vagus nerve on the left side of the neck. Through stimulation of this peripheral nerve, brain function is affected. VNS therapy has been granted marketing clearance by the FDA with an indication for treatment of epilepsy and is being investigated to treat a number of other central nervous system diseases and conditions, such as depression, obesity, Alzheimer's disease, etc.
An obstacle to the broader use of these devices is, in many indications, the lack of a measure of treatment efficacy and knowledge of which patients will respond to treatment. The efficacy of neurostimulation is a function of the settings of the various stimulator parameters (i.e., electrode selection, stimulus pulse amplitude, stimulus pulse frequency, stimulus polarity and stimulus pulse width, among others). However, with the exception of treatment for essential tremor or patients with very frequent epileptic seizures, it is difficult to assess the effect of the stimulus provided and thus difficult to adjust these parameters to achieve the maximum possible treatment efficacy. In addition, some patients will not respond at all to neurostimulation treatment, or the degree of the response may be of a lesser magnitude than desired. Since implantation of a neurostimulator is an invasive surgical procedure and involves significant cost, a priori (pre-implantation) knowledge of the degree to which a specific patient will respond to treatment will be valuable to the patient, his doctors, and third party payers.